1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 66922157, compound

Participants

Reaction Steps

Acetic acid 2-nitro-1-phenethylpropyl ester (180) (10.4302 g, 44.2 mmol) and ethyl isocyanoacetate (4.957 g, 44.2 mmol) were weighed out into a 250 mL round bottom flask. The flask was sealed with a septum, purged with nitrogen, then dissolved in a solution of THF and iso-propyl alcohol (1.6:1, 44 mL, 1M). The reaction was cooled in an ice bath, then DBU (13.6 mL, 2.05 mmol) was added. The reaction was allowed to warm to room temperature, and was allowed to stir at room temperature until judged complete by HPLC (2 h, 25 min.). The reaction was diluted with H2O and diethyl ether, and the organic layer was removed, extracted with 2N HCl, H2O, and NaHCO3. The combined organics were dried with Na2SO4, filtered, and concentrated. The crude product was purified by purified by silica gel chromatography (Combiflash column, 95:5 Hexanes:EtOAc). The product crystallized from the combined Combiflash fractions to obtain a batch of 3.3224 g (29%) of pure 181 and 3.7709 g of 181 containing a small amount of impure material. HPLC: 11.27 min.

Provenance & Evidence